Interplay between Type 2 Transglutaminase (TG2), Gliadin Peptide 31-43 and Anti-TG2 Antibodies in Celiac Disease

Celiac disease (CD) is a common intestinal inflammatory disease involving both a genetic background and environmental triggers. The ingestion of gluten, a proteic component of several cereals, represents the main hexogen factor implied in CD onset that involves concomitant innate and adaptive immune responses to gluten. Immunogenicity of some gluten sequences are strongly enhanced as the consequence of the deamidation of specific glutamine residues by type 2 transglutaminase (TG2), a ubiquitous enzyme whose expression is up-regulated in the intestine of CD patients. A short gluten sequence resistant to intestinal proteases, the α-gliadin peptide 31-43, seems to modulate TG2 function in the gut; on the other hand, the enzyme can affect the biological activity of this peptide. In addition, an intense auto-immune response towards TG2 is a hallmark of CD. Auto-antibodies exert a range of biological effects on several cells, effects that in part overlap with those induced by peptide 31-43. In this review, we delineate a scenario in which TG2, anti-TG2 antibodies and peptide 31-43 closely relate to each other, thus synergistically participating in CD starting and progression.

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Mansonella perstans microfilaremic individuals are characterized by enhanced type 2 helper T and regulatory T and B cell subsets and dampened systemic innate and adaptive immune responses

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0006184 ◽

2018 ◽

Vol 12 (1) ◽

pp. e0006184 ◽

Cited By ~ 6

Author(s):

Manuel Ritter ◽

Winston Patrick Chounna Ndongmo ◽

Abdel Jelil Njouendou ◽

Nora Nganyewo Nghochuzie ◽

Lucy Cho Nchang ◽

...

Keyword(s):

Immune Responses ◽

B Cell ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Mansonella Perstans ◽

B Cell Subsets

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Mucosal Innate and Adaptive Immune Responses against Herpes Simplex Virus Type 2 in a Humanized Mouse Model

Journal of Virology ◽

10.1128/jvi.02584-08 ◽

2009 ◽

Vol 83 (20) ◽

pp. 10664-10676 ◽

Cited By ~ 44

Author(s):

Amanda Kwant-Mitchell ◽

Ali A. Ashkar ◽

Kenneth L. Rosenthal

Keyword(s):

Immune Responses ◽

Lymph Nodes ◽

Humanized Mouse ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Human T Cells ◽

Ifn Γ ◽

Human Immune ◽

Simplex Virus

ABSTRACT Genital herpes, caused by herpes simplex virus type 2 (HSV-2), is one of the most prevalent sexually transmitted diseases worldwide and a risk factor for acquiring human immunodeficiency virus. Although many vaccine candidates have shown promising results in animal models, they have failed to be effective in human trials. In this study, a humanized mouse strain was evaluated as a potential preclinical model for studying human immune responses to HSV-2 infection and vaccination. Immunodeficient mouse strains were examined for their abilities to develop human innate and adaptive immune cells after transplantation of human umbilical cord stem cells. A RAG2−/− γc−/− mouse strain with a BALB/c background was chosen as the most appropriate model and was then examined for its ability to mount innate and adaptive immune responses to intravaginal HSV-2 infection and immunization. After primary infection, human cells in the lymph nodes were able to generate a protective innate immune response and produce gamma interferon (IFN-γ). After intravaginal immunization and infection, human T cells and NK cells were found in the genital tract and iliac lymph nodes. In addition, human T cells in the spleen, lymph nodes, and vaginal tract were able to respond to stimulation with HSV-2 antigens by replicating and producing IFN-γ. Human B cells were also able to produce HSV-2-specific immunoglobulin G. These adaptive responses were also shown to be protective and reduce local viral replication in the genital tract. This approach provides a means for studying human immune responses in vivo using a small-animal model and may become an important preclinical tool.

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